Chronic pain is a debilitating syndrome caused by damage to tissue and the nervous system, arising from trauma and disease. It is poorly served by current drugs. To identify novel more effective therapies we propose to examine the mechanisms underlying this syndrome. We have identified a novel protein which is involved in synaptic plasticity. We will examine its role the development of chronic pain at the cellular level and how it might be exploited for the treatment of chronic pain.
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. Although some of the pathways that code pain in the brain have been defined, it was recently proposed that there also exists a pain-specific pathway in humans. Using human brain imaging, we aim to determine if such a pathway exists and if it is altered in subjects with chronic pain. The existence of such a pathway would significantly aid in the development of better treatment regimes.
A Potential Analgesic Target In A Novel Clinically-relevant Neuropathic Pain Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$685,811.00
Summary
Persistent pain arising from tissue damage, to nerves, muscles or joints for example, is devastating for patients and a huge social and economic burden. This work will investigate one of the pathways that goes awry after sensory nerves are damaged. These experiments will also test whether a drug being developed to treat Alzheimer's disease is effective at blocking the persistent nerve hypersensitivity that sometimes develops after injury.
The Role Of Presynaptic Inhibition In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$466,045.00
Summary
Inhibitory nerve cells in the spinal cord are thought to play an important role in governing the interaction between painful and non-painful stimuli. Defects in this process underlie allodynia, an important symptom of neuropathic pain. We will use recent advances in genetic techniques (optogenetics) to manipulate and study how inhibitory nerve cells separate touch and pain signalling in the spinal cord of normal and neuropathic animals.
Therapeutic Potential Of Glycine Receptors In Pain Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$292,223.00
Summary
Inflammation caused by infection or injury leads to a heightened sensation of pain and can convert non-painful stimuli (e.g., touch) into painful stimuli. This effect is mediated by the production of prostaglandins both in peripheral tissues and in the spinal cord. Prostaglandins have recently been shown to decrease the magnitude of the inhibitory neurotransmission that normally occurs onto pain sensing neurons in the spinal cord. This has the effect of raising the excitability of these neurons, ....Inflammation caused by infection or injury leads to a heightened sensation of pain and can convert non-painful stimuli (e.g., touch) into painful stimuli. This effect is mediated by the production of prostaglandins both in peripheral tissues and in the spinal cord. Prostaglandins have recently been shown to decrease the magnitude of the inhibitory neurotransmission that normally occurs onto pain sensing neurons in the spinal cord. This has the effect of raising the excitability of these neurons, thereby making it easier for weak pain stimuli to be relayed to the brain. Inhibitory neurotransmission onto pain sensing neurons is largely mediated by the alpha3 glycine receptor subunit that is not found anywhere else in the body. Very little is known about the physiological and pharmacological properties of these receptors. We hypothesise that drugs that increase the activation of alpha3 glycine receptors may provide a novel treatment for pain. This project will firstly identify new drugs that can increase the activation of these receptors. It will then test whether these drugs are likely to work in vivo. The project will also establish why these receptors are found only on pain neurons. Together, this information will establish whether alpha3 glycine receptors represent a promising new therapeutic target for inflammatory pain, and will place us in an excellent position to begin the next step of identifying novel therapeutic lead compounds.Read moreRead less
The fundamental problem with pain is that it cannot be seen. We can see injury, but pain and injury are quite often not related. Brain imaging has demonstrated consistent patterns of activity when we feel pain, and long-term changes that happen in chronic, i.e. persistent, painful disorders. This project will use the best technology available to investigate the basics of how our brains perceive pain, and to shed light on some of the brain mechanisms that underpin chronic pain.
Stimulus Induced Synaptic Plasticity In The Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$428,777.00
Summary
Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating ....Acute pain provides important warnings about dangers in our environment. However some clinical conditions produce chronic-persistent pain that outlasts the original injury and its useful role. This persistent pain is a debilitating condition that affects 20% of the Australian population and is characterized by painful sensory experience and a negative emotional state. The clinical management of persistent pain remains problematic due to the intolerable side effects associated with the escalating doses required for adequate pain relief and the limited efficacy of current drug therapies in some clinically important pains states. The persistence of pain after the original injury has resolved suggest the development of adaptations that result in the ongoing pain. The changes in neurobiology underlying persistent pain are poorly defined. A better understanding of this neurobiology will result in better therapeutic approaches to persistent pain. The amygdala is a brain region that is important for pain processing, endogenous analgesia and emotion. A neuronal pathway that delivers information about pain to the amygdala has recently been shown to be critical for the development of persistent pain. Little is known about whether this critical neuronal pathway is modified by pain. This project will determine using electrical and chemical techniques how a brief or persistent painful stimulus changes the delivery of painful information to the neurons in the amygdala. The changes produced by a brief painful stimulus likely represent the initial changes in the development of a persistent pain state. This information may allow us to more fully understand the transition from acute to persistent pain and the changes defined may be sensitive to pharmacological modulation. Preventing or inhibiting these pain induced changes may provide better treatment for persistent pain or ideally prevent people undergoing the transition from acute to persistent pain.Read moreRead less
Excitatory Interneurons: A Sensory Amplifier For Pathological Pain
Funder
National Health and Medical Research Council
Funding Amount
$649,848.00
Summary
Changes to the nervous system during pathological pain remain poorly understood. This poses a barrier to new and more effective pain therapies. We have recently shown that a population of excitatory nerve cells, which express a protein called calretinin, form an amplifier network within the spinal cord that enhances pain signalling. This application will determine how calretinin-positive nerve cells contribute to pathological pain and can subsequently be targeted to provide pain relief.
Pain has a detrimental impact on ones quality of life and a significant financial impact on the community. It has recently been revealed that chronic pain is associated with altered brain anatomy and function. Using human brain imaging, we aim to determine the underlying reason for these changes by following individuals during the development of pain. Defining the mechanism underlying pain will aid in the development of better treatment regimens.
Fibromyalgia: Investigating The Prefrontal Cortex And Its Role In Novel Treatment Approaches
Funder
National Health and Medical Research Council
Funding Amount
$338,110.00
Summary
Fibromyalgia, a chronic pain condition, is experienced by 1-3% of Australians. Despite this high number, the cause of fibromyalgia is still unknown with no effective treatment options. In the proposed investigations I will use state of the art neuroscientific paradigms to explore the brain basis of fibromyalgia and utilise novel brain stimulation protocols to provide long-lasting pain relief.